Endocrine Abstracts

In women, establishment of pregnancy is dependent upon ‘fine-tuning’ of the endometrial microenvironment which is mediated by differentiation (decidualisation) of human endometrial stromal fibroblasts (hESF). Using a robust in vitro model of decidualisation we have demonstrated an important role for local steroid metabolism in regulating hESF, something previously considered a solely endocrine-mediated process. We have conducted detailed time-course profilin...

During the establishment of pregnancy, the endometrium undergoes dynamic remodelling in order to establish a ‘receptive’ microenvironment. Decidualisation, a key part of this process, is characterised by differentiation of endometrial stromal fibroblasts which secrete factors that regulate implantation and placental development. Recent studies in our laboratory have revealed that decidualisation results in altered expression of enzymes that regulate biosynthesis and ...

The human endometrium is a complex multicellular tissue the prime function of which is to provide a receptive environment during a fertile cycle. The tissue responds to steroid hormones exhibiting dynamic cyclical regeneration, angiogenesis, differentiation (decidualisation) and inflammation. In the absence of an embryo the inner surface is shed and repaired without scarring (menstruation). The endometrium exhitbits spatial and temporal expression of androgen receptors (AR) in...

Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is a major risk factor for EC and is associated with elevated cholesterol. 27-Hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an endogenous agonist for Liver X Receptor (LXR) and a selective estrogen receptor modulator (SERM). Exposure to estrogenic ligands increases risk of developing EC however the impact of 27HC on EC is unknown.Samples of stage 1 EC ...

The endometrium is a complex tissue with luminal and glandular epithelial cell layers supported on a multicellular stromal compartment; in women the inner (luminal) portion of the tissue breaks down and is shed during menstruation. The endometrium is exquisitely sensitive to the actions of sex steroids (oestrogens, progestogens and androgens) produced in ovarian and other extra gonadal tissues and delivered via blood vessels that rapidly develop and mature within the tissue (e...

Introduction: Oestrogen receptors (ER) are essential for reproductive function and fertility. ER46 is a 46 kDa truncated isoform of full length ERα (ER66) that binds oestradiol (E2) and can signal via nuclear or membrane-initiated signalling pathways. ER46 has been detected in breast cancer cell lines but expression in endometrial tissues has not been documented. The aims of this study were a) to determine whether endometrial cells express ER46, and b) to investigate a po...

Endometriosis is a chronic hormone-dependent disorder, characterised by growth of ‘ectopic’ endometrial tissue outside the uterus. It has been reported that 30–40% of women who are sub/infertile have endometriosis. Infertility in women with severe endometriosis may be the result of either scarring or pelvic distortion, but in women with mild/moderate disease it is believed subfertility may result from disturbances in endometrial tissue function. Transformation o...

Endometriosis is a hormone-dependent disorder, characterised by growth of endometrial tissue outside the uterus. It has been reported that 30–40% of women with infertility have endometriosis. Transformation of human endometrial stromal fibroblasts (hESC) (termed decidualisation) is accompanied by increased steroid synthesis and is fundamental to the establishment of a receptive endometrial microenvironment, which can support and maintain pregnancy. Evidence suggests that ...

The establishment of pregnancy requires dynamic remodelling of the endometrium. Decidualization, a key part of this process, is characterised by differentiation of endometrial stromal fibroblasts (ESF) which secrete factors that regulate implantation and placental development. We recently discovered that ESF synthesise androgens which modulate the expression of endometrial receptivity and decidualization markers. Utilisation of the circulating androgen precursor DHEA within ta...

The uterus is an androgen-responsive tissue and AR is expressed in cells within the endometrium and myometrium. We have demonstrated that treatment of ovariectomised mice with the potent androgen dihydrosterone (DHT) induces a uterotrophic response with changes in expression of genes involved in cell-cycle progression, Wnt signalling and an expansion of the glandular epithelium. Selective androgen receptors modulators (SARMs) are AR ligands in development as potential therapeu...